1. Inoculation of gamma-interferon (g-IFN)-treated human neuroblastoma cells (SY5Y cells) with Sabin's type-3 live oral poliovirus vaccine (OPV) significantly inhibited viral replication when compared with replication in undifferentiated, untreated cells. Inhibition of viral replication was ten-fold greater for vaccine strains than for revertant neurovirulent strains; a wild-type strain was inhibited even less. This differential sensitivity of poliovirus strains of different levels of attenuation to the effects of g-IFN was not seen in other cell types tested (Hep-2/Cincinnati human heteroploid epithelial cells and WI-38 human diploid fibroblast cells). g-IFN-treated SY5Y cells may provide the basis for an in vitro assay to detect increased neurovirulence of type-3 OPV preparations. 2. A few g-IFN-treated SY5Y cells survived cytolytic effects of polioviral infection. Continued cultivation of those surviving cells established populations in which infection with poliovirus persisted for more than one year. Genetic analyses of viral isolates of persistently infected cultures is underway. This may be relevant to mechanisms of persistent infections with vaccine strains of poliovirus in immunosuppressed subjects and possibly to the post-polio syndrome.